The Ah-receptor (AHR) is a ligand-activated transcription factor found in nearly all vertebrate species examined to date. The AHR mediates an adaptive response to planar aromatic hydrocarbon ligands by up-regulating a battery of genes that ultimately metabolize the ligand molecule. Recently, examinations of AHR knockout mice have revealed that AHR is required for normal vascular development. This second observation suggests that AHR signaling is triggered during development, and that an endogenous signal may activate the AHR. The goal of this project is to identify genes that can activate or inhibit AHR signaling in vivo. By identifying cellular factors that regulate ARR signaling, we may gain insight into the role of this protein in development. We propose that this information will provide insight as to the identity of an endogenous AHR ligand or whether AHR is capable of being activated in the absence of ligand during development.